Presidenza del Consiglio dei Ministri - ITALIAN MICROBIOME INITIATIVE FOR IMPROVED HUMAN HEALTH AND AGRI- FOOD PRODUCTION
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Presidenza del Consiglio dei Ministri
Comitato Nazionale per la Biosicurezza,
le Biotecnologie e le Scienze della Vita
CONCEPT PAPER
ITALIAN MICROBIOME INITIATIVE FOR
IMPROVED HUMAN HEALTH AND AGRI-
FOOD PRODUCTION
2019
1
CONTENTS
1. Summary 3
2. Introduction 4
3. Expertise, infrastructures and industrial sectors involved
in microbiome-based knowledge exploitation 8
3.1 Microbiome Facilities and Expertise 8
3.2 Italian involvement in EU projects and networks 10
3.3 Industrial sectors involved in microbiome-based knowledge exploitation 13
4. Vision: state-of-the-art of knowledge, needs and actions for boosting
the sector in Italy 14
4.1 Knowledge and impacts 14
4.1.1. Microbiome and human health 14
4.1.2 The human gut microbiome and disease prevention and therapy 17
4.1.3. Soils, sediments and sustainable agriculture and food processing 18
4.2 Constrains, needs and opportunities for R&I and policies 24
4.2.1 Microbiome and host health 24
4.2.2. Soils and sediments, Sustainable agriculture, and food processing 30
4.3 Actions required for boosting the microbiome applications in Italy 33
5. Conclusion 34
Working Group 36
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1. Summary
Microbiomes (i.e. Bacteria, Archaea, Eukarya and viruses) are found in humans,
plants, and animals as well as in terrestrial and marine environments, providing benefits to
the planet as a whole and everything that lives on it. Their astonishing metabolic potential
means microbiomes occupy a central position in the “One Health” framework, which
approaches human, animal and plant health from a new integrated perspective that also
encompasses biomedical systems.
Many recent research projects have offered new insights into the associations
between microbiomes and a wide range of human diseases. Scientists are now using this
knowledge to establish balanced conditions of health and to prevent and treat diseases
through the development of personalised approaches and clinical tools. In parallel,
ongoing studies are demonstrating that microbiome structures and dynamics across the
food system (from soils and marine habitats to plants, animals and the foods produced
from them) can have both direct and indirect effects on human microbiomes and health, in
addition to their obvious impact on food quality, safety and sustainability.
Innovative technologies are providing us with more detail about microbiota. A
multidisciplinary approach integrating these technologies gives us more information about
the humans, plants and animals with which these microbes live in symbiosis. Microbiomes
are emerging from the available studies as highly dynamic, changeable and adaptable
systems. Further research is needed to fully clarify the interplay between microbiomes and
environmental, nutritional and host variables.
To date, under FP7 and H2020 the European Commission has funded 216 projects
to the tune of approximately €500 million to advance knowledge in this area (Hadrich,
Front Genet, 2018). However, Italy’s role in this major EU-wide effort has so far been
minor. Italian researchers have considerable expertise in the preclinical and clinical
investigation of human microbiomes and viromes and in the study of microbiomes in the
soil, plants, land and aquatic animals and foods and their relationship with the human gut
microbiome and health. Nonetheless, their activity is largely fragmented and its social and
economic impacts lower than should be expected. The main reason for this is that unlike
other EU countries, Italy does not have a state- funded microbiome programme and this
area is not a key priority in the national research plan or in the Italian technology clusters’
strategic R&I agendas. It is now imperative to promote a national plan for research on
human, animal, plant and food microbiomes with the main objectives of:
i) improving knowledge;
ii) improving exploitation of natural resources;
iii) sharing expertises and infrasctructures; and
iv) ensuring their efficient use in promoting health.
This will require a coordinated national initiative to assess the areas in which Italy’s
existing knowledge, resources and biobanks might give it an advantage over other
countries.
This should be done by:
a) establishing a national network of experts and public and private organizations
working in the sector in order to pool the existing national data, knowledge, infrastructure
and skills;
b) fostering cooperation between public and private sectors, in close cooperation with
the Italian health and agri-food technology clusters, to maximize the leverage effects of
public and private investments;
c) planning and implementing joint regional and national R&I initiatives and policies
by promoting investment in R&I and spin-offs/start-ups and facilitating their interconnection
with international networks, to encourage the application of microbiome know-how as well
as to promote best practices, standards and consistent protocols;
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d) promoting researcher careers, training and mobility and the development of skills
in the different microbiome domains; and
e) exchanging knowledge across the scientific and political community and ensuring
the efficient use of the available resources, while advocating public understanding of the
value of microbiomes for the health of the planet and all the humans, plants and animals
that live on it.
2. Introduction
Complex microbial ecosystems, collectively referred to as microbiomes, inhabit and
interact with living organisms and have co-evolved a range of symbiotic relationships with
them, including mutualism, with ultimate beneficial outcomes for the host.
Due to their astonishing metabolic potential, microbiomes have a key role in human,
plant, animal and, ultimately, planetary health, and occupy a central position in the “One
Health” framework, contributing to a new integrated perspective of the health of living
organisms (Figure 1).
Figure 1. The One Health framework offers a new integrated view of how
microbiomes contribute to human, animal and plant health.
The microbial ecosystem most explored to date is undoubtedly the microbiome of the
human gut. The microbes in our gastrointestinal tract are ten-fold more numerous than all
the cells that make up the human body (Figure 2) and include components from all three
domains of life, i.e. Bacteria, Archaea and Eukarya, and their viruses.
4
Figure 2. Estimated size of the human microbiota (the community of all
microorganisms found in the human body) and of the human microbiome (the collective
genomes of resident microorganisms in the human body).
This microbial community interacts constantly and extensively with the host at the
intestinal mucosal surface and plays fundamental roles in several aspects of our
physiology that are instrumental to the maintenance of metabolic and immunological
homeostasis. Intestinal microorganisms are involved in the bioconversion of dietary
components, leading to the production of a wide and diverse range of bioactive small
molecules, including short-chain fatty acids (SCFAs), vitamins, amino acid metabolites,
neurotransmitters and phytoestrogens, and interkingdom sensing molecules. They are
thus fundamental to host nutrition, the function of the immune, endocrine and central
nervous systems and protection against pathogenic colonization (Tilg and Moschen,
Gastroenterology 2015; Sonnenburg and Bäckhed, Nature 2016). The crosstalk between
the gut microbiome and the immune system is widely recognized as critical to human
health (Honda and Littman, Nature 2016; Thaiss et al., Nature 2016). The gut microbiome
has in fact been considered a “forgotten” endocrine organ that acts as an endogenous
circadian organizer and a key regulator of the central nervous system, with an ultimate
capacity to modulate our behaviour and contribute to the pathophysiology of neurological
disorders (Neuman et al., FEMS Microbiol Rev 2015; Sharon et al., Cell 2016; Thaiss et
al., Cell 2016; Tremlett et al., Ann Neurol 2017). The individual gut microbiome may also
affect the metabolism of xenobiotics, including drugs, with potentially important
repercussions for their pharmacokinetic profile (Spanogiannopoulos et al., Nat Rev
Microbiol 2016).
The intestinal microbial communities are inherently dynamic and can fluctuate
between different states of eubiosis over time. These fluctuations are closely linked to the
person’s path through life and the communities maintain a mutualistic relationship with
their human host that is essential for homeostasis and health (Halfvarson et al., Nat
Microbiol 2017). However, when challenged with various endogenous (e.g. Toll-like
receptor polymorphisms) and/or environmental stressors, the composition and function of
the gut microbiota may change considerably, resulting in a “dysbiotic” profile that
compromises mutualism and may trigger or consolidate a disease state. There is in fact
mounting evidence on the role of the gut microbiome in a number of enteric and systemic
disorders, including gastrointestinal, metabolic, hepatic, autoimmune, respiratory,
cardiovascular, neurological and even oncological diseases, often referred to as non-
communicable diseases (NCDs) (Lynch and Pedersen, N Engl J Med 2016) (Figure 3).
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Figure 3. There is mounting evidence on the role of the gut microbiome in a number
of enteric and systemic disorders.
Microbiome-disease associations typically involve the loss of beneficial, health-
associated microbes (mostly producers of SCFAs), the bloom of opportunistic pathogens,
or a broad restructuring of the gut microbial ecosystem, with clinically significant or even
life-threatening consequences (Duvallet et al., Nat Commun 2017). Recent extensive
surveys and meta-analyses exploring variations in the human gut microbiome in health
and disease revealed that even microbiome dysbioses are highly personalized and follow
distinctive temporal changes. A greater understanding of these could help guide more
knowledge-based personalized intervention strategies (Zaneveld et al., Nat Microbiol
2017; Koskella et al., Nat Ecol Evol 2017). The loss of the microbiota-host equilibrium may
also contribute to the onset of “pre-disease” states (pre-diabetes, pre-hypertension, etc.)
and thus play a part in the rise of NCDs (van de Guchte M et al., Microbiome 2018).
Studies characterizing the gut microbiome in thousands of people, in parallel with
covariates assessing health status, diet, lifestyle, medication, biomedical parameters and
genetics (Falony et al., Science 2016, Wang et al., Nature Genetics 2016; Rothschild et
al., Nature 2017), have demonstrated that these determinants explain only a small fraction
of the total gut microbiome variation and that we are still missing important covariates
when assessing drivers of this variation (Figure 4).
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Figure 4. The human gut microbiome has been the subject of extensive research,
which has established its involvement in metabolism, nutrition, physiology and immune
function. Determinants such as health status, age, environment, hormones, supplements
and drugs explain only a small fraction of the total gut microbiome variation and its
involvement in health and disease.
The microbial communities of diverse anatomical sites, ranging from more obvious
sites such as the skin and the genitourinary tract, to less obvious ones such as the
airways, have now been characterized. Areas that were previously considered to be
absolutely devoid of microorganisms, such as the placenta and the fetus, have also been
characterized (Cao et al., 2014, Mor and Kwon, Am. J. Obstet. Gynecol., 2015). This
broader perspective suggests that novel, previously neglected drivers of human gut
microbiome variation could be sought using the One Health theoretical framework. These
could include covariates in animal, plant and environmental domains that have never been
explored. It is known, for instance, that microbiome structures and dynamics across the
different components of the food system (soil, sediments, plants and animals, feed, food,
farms, processing, workers and consumers) can directly and indirectly affect human
microbiomes in many ways. For example, the soil/rhizosphere microbiome mediates the
cycle of carbon and other nutrients, affects the maintenance of soil fertility and carbon
sequestration, and sustains plant growth (Fiorilli et al., Sci Rep 2018; Bulgarelli et al., Cell
Host Microbe 2015). At the same time, animals host diverse microbial communities that
have evolved alongside them and play crucial roles in their biology and health (Walter and
Ley, Annu. Rev. Microbiol., 2011, Hooper et al., Science, 2012) as well as in dairy and
meat product fermentation processes. These activities have direct and indirect effects on
both plant and animal growth and health in terrestrial and marine ecosystems and hence
affect the quantity, quality and sustainability of primary production (Amundson et al.,
Science 2015) and food processing, and, in turn, their final impact on human health.
Plants play a crucial role too, as they also possess their own microbiota, which has a
strong influence on their health. Many physiological plant functions require the presence of
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these mostly benign microbes and the establishment of specific plant–microbe
relationships (Ash and Mueller, Science, 2016; Bonfante and Genre, Nat. Commun.,
2010). Hence, looking at microbiota from a One Health perspective, there are numerous
important cofactors with closely interwoven relationships.
By far the greatest part of our current knowledge of microbiomes concerns bacteria.
However, viruses are now receiving increasing attention, as they have been found to fill a
variety of ecological niches within their host. Host-virome interactions can no longer be
limited to a view of viruses as pathogens. Members of the eukaryotic virome that
chronically infect both mammals (including humans) and plants have been found to exert
significant effects on host physiology, far beyond the simple paradigm of invasion and
tissue destruction (Foxman et al., Nat Rev Microbiol 2011; Stelekati et al., Cell Host
Microbe 2012; Virgin et al., Cell 2009).
Unlike some other EU countries, Italy does not have any state-funded national
microbiome programme. Despite this, Italian researchers are active in various studies of
microbiomes. These include preclinical and clinical studies of the human microbiome in
various parts of the body, to characterize its role in physiological and pathological
conditions in infants, children, adults and the elderly; investigation of the human virome;
and investigation of the microbiome of soil, sediments, crops, aquatic plants and animals,
and foods, and their relationship with human gut microbiome and health. However, their
efforts are largely fragmented, limiting the potential contribution of their work to
international knowledge of the microbiome and how it can be exploited. There is thus an
urgent need for a coordinated national initiative.
3. Expertise, infrastructures and industrial sectors involved in microbiome-
based knowledge exploitation
3.1 Microbiome Facilities and Expertise (Figure 5) rely on the genome-based
analyses, resources and support needed to characterize and study microbiomes,
including:
1. Advanced technological platforms for their phylogenetic and functional
characterization, including next-generation sequencing (NGS) platforms such as Miseq,
NextSeq and HiSeq (Illumina), Ion Torrent PGM (Life Technologies) and PacBio (Pacific
BioSciences) that allow researchers to:
- rapidly sequence whole microbial genomes and metagenomes, enabling an
overview of their functional capabilities;
- use RNA sequencing (RNA-Seq) for metatranscriptomic analysis.
2. Quantitative Real-Time PCR platforms for quantification of nucleic acids in
different applications, for gene expression, genotyping, copy number variation, microRNA,
pathogen detection, etc.
3. Proteomics platforms, including LC-MS/MS Orbitrap to quantify meta-
proteomes and specific metabolic pathways.
4. Metabolomics platforms: LC-MS/MS Quantum Access MAX triple quadrupole
mass spectrometer coupled to U-HPLC, LC-MS/MS Orbitrap and NMR 600 Hz for
host/microbiome metabolomic profiling, quantification of microbiome metabolites and co-
metabolites, measurement of trace-level environmental or food contaminants and
detection of specific biomarkers.
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5. Phenotype Microarray platform (e.g. OmniLog®) for genotype-phenotype
characterization of microbes and determination of the optimal conditions for cell growth,
sporulation and germination, production of secondary metabolites and enzymatic activities
in cell lines.
6. Simulator of the Human Intestinal Microbial Ecosystem (e.g. SHIME®) to
mimic the human gastrointestinal digestion in vitro. SHIME is one of the few gut models
that simulates the entire gastrointestinal tract, incorporating the stomach, small intestine
and different colon regions.
7. Microbial biobanking, under the umbrella of the pan-European research
infrastructure MIRRI (Microbial Resource Research Infrastructure), for suitable long-term
preservation of microbial isolates.
8. Plant facilities to mimic and predict the impact of climate change on crop
production (e.g. FACE laboratory in open field).
9. Animal Facilities to perform studies in animal models (e.g. mice and rats).
Authorized facilities are available for the conduct of specific challenge models in controlled
conditions, as are infrastructures to produce germ-free and specific pathogen-free animals,
facilities for the conduct of small and mid-scale trials in farm animals (e.g. pigs, poultry,
dairy cows and goats), and experimental tanks for aquaculture studies.
10. High-performance computers (HPCs) and infrastructure as essential tools to
organize and exploit big databases for microbiome knowledge.
11. Databases and bioinformatics pipelines for metataxonomic and metagenomic
data analysis, and multidimensional statistical approaches for the integration of
microbiome datasets, host phenotyping and environmental metadata, from a systems
biology perspective.
12. Human, animal and plant model phenotyping: body composition analysis
(dual-energy X-ray absorptiometry, bioimpedance analysis, air displacement
plethysmography), energy expenditure evaluation (indirect calorimetry, movement
actigraphy), energy and nutrient intake (eating pattern and behaviour evaluation), and
functional assessment (handgrip and leg-extension strength tests, submaximal exercise
test, physical performance battery).
13. Platforms for controlled microscale food fermentation, to determine the
dynamics of controlled fermentation of food products under different operating conditions
and microbiome configurations.
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Figure 5. Some of the Microbiome Facilities and Expertise used to characterize and
study microbiomes.
Based on: Al Khodor S, Reichert B and Shatat IF (2017) The Microbiome and Blood
Pressure: Can Microbes Regulate Our Blood Pressure? Front. Pediatr. 5:138. doi:
10.3389/fped.2017.00138
3.2. Italian involvement in EU projects and networks
Italian researchers have participated in or are currently contributing to a number of
past and ongoing collaborative EU projects dealing with nutrition, microbiome and human,
animal and plant host health, as summarized below.
Nutrition and host health
• “New dietary strategies addressing the specific needs of elderly population for a
healthy ageing in Europe” (NU-AGE) consortium: a collaborative project for the
development of functional food prototypes and the improvement of traditional foods
tailored for the elderly; https://cordis.europa.eu/result/rcn/155983_it.html
(COORDINATION)
• “European network on the factors affecting the gastro-intestinal microbial balance
and the impact on the health status of pigs” (PiGutNet) consortium: a collaborative project
for genome/metabolome-wide association studies and the provision of a road map to
increase pig resistance against GIT infections. COST Action FA1401;
http://www.pigutnet.eu/ (COORDINATION)
10• "Ecology from farm to fork of microbial drug resistance and transmission"
(EFFORT) consortium: collaborative project to inform decision makers, the scientific
community and other stakeholders about the consequences of anti-microbial resistance in
the food chain; https://cordis.europa.eu/project/rcn/111140_it.html
• "Reducing egg susceptibility to contaminations in avian production in Europe"
(RESCAPE) consortium: collaborative project for the reduction of food safety risks by
optimizing hen cages and egg collection management;
https://cordis.europa.eu/project/rcn/80032_it.html
• "European animal disease genomics network of excellence for animal health and
food safety" (EADGENE) consortium: collaborative project for strengthening the
implementation of durable integration in FP6 Networks of Excellence;
https://cordis.europa.eu/project/rcn/74158_en.html
• "Interplay of microbiota and gut function in the developing pig – Innovative
avenues towards sustainable animal production" (INTERPLAY) consortium: collaborative
project for the improvement of animal health and food safety through investigating the gut
function of farm animals, the gastro-intestinal microflora and their interactions;
https://cordis.europa.eu/project/rcn/92294_en.html
• "Connecting the animal genome, gastrointestinal microbiomes and nutrition to
improve digestion efficiency and the environmental impacts of ruminant livestock
production" (RUMINOMICS) consortium: collaborative project for the development of
models and tools to enable the livestock industry to reduce environmental damage from
methane and nitrogen emissions and to improve feed efficiency;
https://cordis.europa.eu/project/rcn/101163_it.html
• "The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD)"
(FLORINASH) consortium: collaborative project addressing the role of intestinal microflora
activity in the pathogenesis of NAFLD; https://cordis.europa.eu/project/rcn/93672_en.html
• "New E-Services for a dietary approach to the elderly" (RISTOMED) consortium:
collaborative project addressing the common problem of delivering innovative
nutraceuticals for the control and prevention of age-related diseases;
https://cordis.europa.eu/project/rcn/92439_en.html (COORDINATION)
• "Metagenomics of the Human Intestinal tract" (METAHIT) consortium:
collaborative project to establish associations between the genes of the human intestinal
microbiota and our health and disease; https://cordis.europa.eu/project/rcn/87834_en.html
• "Microbiome Influence on Energy balance and Brain Development-Function Put
into Action to Tackle Diet-related Diseases and Behaviour" (MyNewGut) consortium:
collaborative project for the development of new approaches to prevent diet-related
diseases and behavioural disorders through lifestyle changes and dietary interventions
with new food products; https://cordis.europa.eu/project/rcn/111044_it.html
"Genomic and nutritional innovations for genetically superior farmed fish to
improve efficiency in European aquaculture" (AquaIMPACT) consortium: collaborative
project responding to the need for innovative feed formulations for fish reared in
aquaculture systems; Horizon 2020. Call: H2020-BG-2018-2020 (Blue Growth) Topic: DT-
BG-04-2018-2019; Type of action: IA
MIC CERES international project: Microbial eco-compatible strategies for
improving wheat quality traits and rhizospheric soil sustainability.
Food processing
• "Controlling Microbiomes Circulations for Better Food Systems” (CIRCLES)
consortium: collaborative project to discover, translate and communicate innovative,
microbiome-based applications to enhance food system performances and their
sustainability; H2020-SFS-2018 (COORDINATION)
11 "Sustainable innovation of microbiome applications in food system” (SIMBA)
consortium: Innovative action to harness complex soil and marine microbial communities
(microbiomes) for the sustainable production of food. This project has just been accepted
for a 4-year period in response to call LC-SFS-03-2018 "Microbiome applications for
sustainable food systems”.
“Microbiome applications for sustainable food systems through technologies and
enterprise” (MASTER) consortium. This project has just been accepted in response to call
LC-SFS-03-2018 "Microbiome applications for sustainable food systems”.
“SOURDOugh biotechnology network towards novel, healthier and sustainable
food and bIoproCesseS” (SOURDOmICS) consortium. This project has just been
accepted in response to call OC-2018-1 “RP3 Towards a sustainable future, the aim of the
present: a focus on Agriculture, Biological sciences, Environment and Chemistry. COST
action.
• “Biotransformation of brewers’ spent grain: increased functionality for novel food
applications” (FUNBREW) consortium: collaborative project to establish bioprocessing
technologies for the synthesis in situ of functional compounds in BSG, such as
exopolysaccharides (EPS) and antioxidants. COST ACTION 2017.
https://tuhat.helsinki.fi/portal/en/projects/biotransformation-o(ea2896e5-a08a-4cd4-a131-
ddc6faf52098).html
• "Inflammatory Bowel Disease: an EU-NZ integrated approach for characterizing its
molecular multifactorial mechanisms" (REINFORCE) consortium: collaborative project
aiming to improve the understanding of IBD and train the scientists involved and expand
on their technical knowledge; FP7- PEOPLE.
https://cordis.europa.eu/result/rcn/165580_en.html
• "Novel multifunctional plant protein ingredients with bioprocessing" (BIOPROT)
consortium: collaborative project to boost scientific cooperation between EU member and
associated states in order to maximize the contribution of research to the development of
more sustainable food systems; FP7-ERANET-2011-RTD. https://www.era-
learn.eu/network-information/networks/susfood/1st-joint-call-for-proposals/novel-
multifunctional-plant-protein-ingredients-with-bioprocessing
• "Innovative biotechnological solutions for the production of new bakery functional
foods" (Bake4Fun) consortium: collaborative project to respond to the needs of food
SMEs for innovative food formulations and technologies to overcome the negative effect of
iron fortification of bakery products; FP7-SME-2013.
https://cordis.europa.eu/project/rcn/110204_it.html
Soils, sediments and the rhizosphere
• "Unravelling and exploiting Mediterranean Sea microbial diversity and ecology for
xenobiotics’ and pollutants’ clean up" (ULIXES) consortium: collaborative project aimed at
the bioremediation of the Mediterranean Sea by exploring its microbial diversity – SICA;
FP7 https://cordis.europa.eu/project/rcn/97824_it.html (COORDINATION)
• "Marine microorganisms: cultivation methods for improving their biotechnological
applications" (MACUMBA) consortium: collaborative project to improve the isolation rate
and growth efficiency of marine microorganisms from conventional and extreme habitats
and the use of automated high throughput procedures; FP7
https://cordis.europa.eu/project/rcn/104389_it.html
"Linking belowground biodiversity and ecosystem function in European forests"
(Biolink) consortium: collaborative project to fully explain the connection between
diversity, stability and ecosystem function - COST ACTION FP1305 (2013-2018);
http://www.cost.eu/COST_Actions/fps/FP1305
12• "Industrial applications of marine enzymes: innovative screening and expression
platforms to discover and use the functional protein diversity from the sea" (INMARE)
consortium: collaborative project to streamline the pathways of discovery and industrial
applications of new marine enzymes and bioactives for the targeted production of drugs
and fine chemicals; H2020 https://cordis.europa.eu/project/rcn/193292_it.html
• "Marine Microbial Biodiversity, Bioinformatics and Biotechnology" (MICRO B3)
consortium: collaborative project for the development of innovative bioinformatic
approaches to make large-scale data on marine viral, bacterial, archaeal and protists
genomes and metagenomes accessible for marine ecosystems biology and to define new
targets for biotechnological applications; FP7
https://cordis.europa.eu/project/rcn/101555_en.html
• "Increasing Value and Flow in the Marine Biodiscovery Pipeline" (PHARMASEA)
consortium: collaborative project for the production of new products with desirable
characteristics for development by SME partners in three accessible market sectors,
health (infection, inflammation, CNS diseases), personal care and nutrition; FP7
https://cordis.europa.eu/project/rcn/104338_it.html
• "DEVelopment Of innovative Tools for understanding marine biodiversity and
assessing good Environmental Status" (DEVOTES) consortium: collaborative project for
the development, testing and validation of innovative integrative modelling tools to further
strengthen our understanding of ecosystem and biodiversity changes; FP7
https://cordis.europa.eu/project/rcn/105613_en.html
• “Biotechnology from desert microbial extremophiles for supporting agriculture
research potential in Tunisia and Southern Europe” (BIODESERT) FP7 report
https://cordis.europa.eu/project/rcn/93561_en.html (COORDINATION)
3.3 Industrial sectors involved in microbiome-based knowledge exploitation
The knowledge generated around microbiomes is now attracting the interest of
several industries, which need to be engaged to effectively and responsibly apply this new
knowledge. The National Technology Clusters CLAN (Agri-Food) and ALISEI (Life
Sciences) are supporting initiatives to open up ways to modify microbiomes and develop
microbiome-based applications.
Biotechnology industry
Several recently established companies aim to develop new therapies that alter
the microbiome for the benefit of human health. For instance, probiotics and prebiotics are
now in common use and are routinely included in foods, drinks and supplements.
Pharmaceutical and diagnostic industry
The development of alternative interventional measures (prophylaxis/prevention or
treatment) to limit antimicrobial use has a high translational potential. The development
and validation of modulators of host immunity and/or microbial ecosystems, feed additives
and novel molecules are key research targets. Inter-sectorial collaboration could open new
avenues for the exploitation of residual bioactive compounds and agro-industry by-
products.
A major expectation for microbiome research is the identification of biomarkers to
enable the reclassification of comorbidities by their mechanism and the development of
new therapeutic strategies. New validated biomarkers will greatly facilitate the
management of metabolic diseases and their comorbidities by providing new possibilities
13for diagnostic and predictive medicine and qualified strategic therapies, thus paving the
way for a new direction in clinical research on new targets.
New diagnostic tools and methods for point-of-care diagnostics, cheap, user-
friendly innovative devices, high throughput microbial detection and characterization and
antibiotic resistance monitoring.
Food industry
The food we eat, and the way we eat it, are changing. The consumption of processed
foods with longer shelf lives and ready-to-eat foods is on the rise, and snacking is
becoming ever more dominant. At the same time, the human population is rapidly
expanding and the great challenge is now sustainable agriculture. The combination of
these forces is creating a need for sustained innovation in the identification of affordable
new food sources and highly nutritious foods. Studies of microbiomes could help in the
integration of agricultural policies and practices, food production and distribution and
nutritional recommendations for consumers of different ages, lifestyles, geographies and
states of health.
Agro-industry: primary production
Plant and animal microbiomes can be manipulated for a more sustainable production
of high-quality foods by modulating plant and animal growth, controlling their physiological
development, boosting their defences against pathogens and insect pests, improving their
nutrient quality and controlling resistance to stress.
4. State-of-the-art, research requirements and actions needed to boost the
sector in Italy
4.1. Knowledge and impact
4.1.1. Microbiome and human health
Microbiomes colonize a number of different body regions including the nose, mouth,
throat, skin, vagina, urethra and intestine. To date, the gut microbiome has received the
most attention. Its immense gene catalogue is almost 3 orders of magnitude larger than
that of the human body, and it has a profound influence on human physiology and
metabolism. Gut microorganisms complement several gaps in human metabolic pathways,
producing essential vitamins (mainly B vitamins) and enabling energy to be extracted from
otherwise indigestible carbohydrates (dietary fibre), thus playing a major role in host
energy balance and nutrition. Intestinal microbes are also involved in the bioconversion of
dietary components, with major effects on immune functionality and metabolic
homeostasis (Tilg and Moschen, Gastroenterology 2015; Sonnenburg and Bäckhed,
Nature 2016).
It is therefore not surprising that several metabolic disorders, including obesity, type 2
diabetes and NAFLD, are associated with microbiome dysbiosis. The altered pattern of
bacterial taxa and microbiome-derived biomolecules this entails may promote or further
aggravate disease processes (Hartstra et al., Diabetes Care 2015; Tripathi et al., Nat Rev
Gastroenterol Hepatol 2018). For example, the dysregulation of the microbiota-host co-
metabolism of bile acids may impair glucose homeostasis and liver and pancreatic function
and lead to adipose tissue inflammation (Wahlström et al., Cell Metab 2016). High-fat, low-
fibre Western diets have been repeatedly shown to affect the gut microbiome structure,
with detrimental effects on intestinal permeability, lipid accumulation and inflammatory
14state (Jena et al., FASEB J 2018). In contrast, a Mediterranean-style diet with a higher
intake of high-fibre food is known to beneficially modulate host-microbiome interactions,
helping to prevent a number of diseases (De Filippis et al., Gut 2016) (Figure 6).
Figure 6. Microbiota-host transgenomic metabolism and its impact on human health
(GM: gut microbiome)
However, the health-promoting features of the gut microbiome as shaped by the
Mediterranean diet require further investigation.
Recent evidence suggests that physical activity has a role in the modulation and
shaping of gut microbiomes (Cronin et al., mSystems 2018; Greenhill et al., Nat Rev
Endocrinol 2018).
Metagenomic analysis in obese Italians has revealed specific signatures associated
with different metabolic traits. An interplay has been demonstrated between increased
proteobacteria and phenylacetic acid, a microbial metabolite that interferes with branched
chain amino acid catabolism (Hoyles et al., Nature Medicine 2018). In subjects with
glucose intolerance, derangements in microbial tryptophan metabolism have been
observed, with a specific induction of metabolites of the kynurenine pathways and a
reduction in indoles (Laurans et al., Nature Medicine 2018).
The gut microbiota is widely recognized as an integral component of the human
immune system, finely calibrating both innate and adaptive immune responses throughout
life. The intimate interplay between gut microbes and mucosal immune cells is crucial for
the maintenance of immune homeostasis and, above all, for the education of the immune
system during infancy (Honda and Littman, Nature 2016; Thaiss et al., Nature 2016).
Specific gut microbiome alterations in the first months of life, a critical time window for
long-term health, have been associated with the development of allergy and other
immunological/metabolic disorders later in life (Arrieta et al., Sci Transl Med 2015; Cox et
al., Cell 2014). Regardless of age, disruption of the delicate balance of commensal
bacteria (dysbiosis) may lead to impaired local and systemic immune responses, with
breakdown of mucosal barriers, translocation of gut bacteria beneath the epithelium and a
change in the cytokine milieu and T cell ratio towards an inflammatory phenotype, thus
eliciting a profound inflammatory state both locally and systemically (Gopalakrishnan et al.,
Cancer Cell 2018) (Figure 7).
15Figure 7. Interaction between diet, microbiota and immune response at mucosal
sites. A. To maintain a healthy state, the local microbiota and mucosal immune system are
in homeostasis at mucosal sites. The microbiota educates and promotes the maturation of
the immune system by inducing pro-inflammatory and anti-inflammatory immune cells; B.
During pathological conditions, such as inflammatory bowel disease and asthma, the
homeostasis at the mucosal barrier is disrupted.
Based on: Statovci D, Aguilera M, MacSharry J and Melgar S (2017) The Impact of
Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal
Interfaces. Front. Immunol. 8:838. doi: 10.3389/fimmu.2017.00838
This is the case with several NCDs whose common basis is inflammation, including
inflammatory bowel disease and irritable bowel syndrome. It is also seen in other disorders
with a strong immunological component. In autoimmune diseases such as type I diabetes
and rheumatoid arthritis, the host can no longer control commensal bacteria, while in
immunosuppressive diseases such as HIV infection, or in patients with or undergoing
haematopoietic stem cell transplantation for blood cancers, it may enable pathogen
invasion and infection (Lynch and Pedersen, N Engl J Med 2016; Zaneveld et al., Nat
Microbiol 2017).
Mounting evidence on the bidirectional gut-brain axis also supports the role of the
intestinal microbiome in the regulation of anxiety, cognition, pain and behaviour and its
possible contribution to the pathophysiology of central nervous system disorders, such as
multiple sclerosis, autism spectrum disorders and major depression (Sharon et al., Cell
2016). The gut is the largest nervous system outside the CNS that is autonomously active
and in close interplay with its microbiota. This enteric nervous system is also called “the
second brain”.
The microbiota has been shown to influence multiple aspects of
neuropathophysiology, including neurotransmission and the behaviours often associated
with neuropsychiatric conditions, such as anxiety and depressive-like behaviours (Kim et
al., Curr Neuropharmacol 2018). In addition, convincing evidence points to a malfunction
16of the intestinal barrier as the mechanism underlying the immune dysfunction that
ultimately leads to neurological disorders such as the demyelinating lesions seen in
multiple sclerosis (Camara-Lemarroy et al., Brain 2018). There is also mounting evidence
on the role of the microbiota-gut-brain axis in neurodegenerative conditions (including
Parkinson’s disease, multiple sclerosis, Alzheimer’s disease and amyotrophic lateral
sclerosis) and psychiatric disorders (including anxiety, depression, schizophrenia and
autism spectrum disorders) (Sampson et al., Cell 2016; Pellegrini et al., Acta
Neuropathologica 2018). Recent experimental and clinical investigations have also shown
that the gut microbiota influences the outcome of cerebral ischemia (Singh et al., J Cereb
Blood Flow Metab 2018). In addition, the functional output of the gut microbiome, including
SCFAs and amino acids, and the microbiome’s ability to alter the bioavailability of aromatic
and branched chain amino acids, confirm the existence of a gut-muscle communication
pathway and seem to be involved in the mechanisms leading to the development of
sarcopenia, sarcopenic obesity and, possibly, cancer cachexia (Picca et al., Mediators
Inflamm 2018; Ticinesi et al., Nutrients 2017; Inglis et al., Curr Osteoporosi Rep 2015;
Klein et al., Curr Opin Support Palliat Care 2013).
4.1.2 The human gut microbiome and disease prevention and therapy
There is an urgent need to translate the data and knowledge on the gut microbiome
generated in recent years into concrete actions. The growing body of literature on the
transition of the human gut microbiota from health to disease will help in the design of
knowledge-based, personalized intervention strategies to manipulate the intestinal
microbial community towards a more “favourable” profile, enabling an enhanced
therapeutic response. These strategies will include:
i) dietary interventions, as a simple, safe and accessible adjunct to current therapies;
ii) administration of bacterial consortia or “designer probiotics”, selected on the basis
of the growing understanding of the complex syntrophic connections between microbiota
components and the dysbiosis in question; and
iii) faecal microbiota transplantation, as the most direct means of manipulating an
impaired gut microbiome.
Future research will have to take into account the inherent variability of the gut
microbiome by monitoring the individual trajectory over time in states of eubiosis and
dysbiosis. Similarly, novel, microbiome-specific endpoints must be implemented to assess
the efficacy of a given probiotic therapy. The success of a probiotic course depends on the
supported recovery of a state of microbiome eubiosis and hence on the probiotics’ ability
to redirect the individual dysbiotic trajectory to within the range of normal variation (“the
healthy plane” – Halfvarson et al., Nat Microbiol 2017; Zaneveld et al., Nat Microbiol 2017).
Re-analysis of the gut microbiome at the end of any probiotic course will thus be essential
to evaluate their efficacy in terms of recovery of a healthy microbiome configuration.
Culturomics, an approach that aims to cultivate all the components of the human gut
microbiome through the use of optimized selective and/or enrichment culture conditions
coupled with metagenomic identification, is expanding the narrow range of probiotics
currently available to consumers. Other microorganisms are being revealed as providers of
new, more effective probiotic functions - the “next-generation probiotics” (O’Toole et al.,
Nat Microbiol 2017; Kim et al., Crit Rev Food Sci Nutr 2018). For example, the bacteria
Christensenella and Faecalibacterium prausnitzii show a greater anti-inflammatory
potential than the traditional bifidobacteria and lactobacilli, while Akkermansia muciniphila
has promising potential for the treatment of obesity. Human microbiomes are also
receiving significant attention thanks to their influence on cancer therapy. Several recent
studies have demonstrated the existence of a “more favourable” gut microbiome
configuration predictive of a positive long-term response, strongly suggesting that
17manipulating the gut microbiota could be an important adjunct to current multimodal
therapeutic anti-cancer strategies to improve response and circumvent primary resistance,
disease recurrence and treatment toxicity (Gopalakrishnan et al., Cancer Cell 2018;
Thomsen et al., Benef Microbes 2018; Pouncey et al., Ecancermedicalscience 2018;
Viaud et al., Oncoimm 2018).
In any case, despite the many advances in metagenomics achieved in recent years,
the human gut microbiome still harbours a large amount of uncharacterized functional
diversity, with an immense potential for the discovery of new health-promoting biological
molecules. Such molecules could offer innovative possibilities in medicinal chemistry,
leading towards the identification of novel drug candidates and targets and more generally,
new ways to treat unmet medical needs. Microbiota-derived metabolites are now emerging
as promising starting hit compounds to modulate human targets, hence triggering certain
pharmacological responses. Robust campaigns of metagenome-based microbiome
bioprospecting that synergize complementary approaches (such as functional omics,
systems medicine, in silico drug discovery, target fishing and quantum biomolecular
modelling) must thus be prioritized to enable the implementation of innovative, precise
strategies to steer the contribution of the gut microbiome towards human health. At the
same time, increasing knowledge of the impact of the microbiome on pharmacokinetics
and hence on individual drugs is instrumental to the implementation of specific approaches
of rational drug design. These are aimed at removing or modifying chemical and functional
groups known to undergo microbial metabolism in the gut, in order to increase drug
bioavailability and reduce drug toxicity. Research in this direction will enable the best
intervention strategies to be established in line with the individual gut microbiome
functional configuration, for more precise, knowledge-based and cost-effective drug use.
4.1.3. Soils, sediments and sustainable agriculture and food processing
Relevance of primary production and food processing for the Italian economy.
In 2017, the Italian food industry in 2017 had a turnover of 137 billion euros
(approximately 32 billion euros from exports) and involved 385,000 employees and 58,000
companies, making it the second largest manufacturing sector in Italy. It is also the third
largest food industry in Europe, behind Germany and France (Italian bioeconomy strategy
http://www.agenziacoesione.gov.it/opencms/export/sites/dps/it/documentazione/S3/Bioeco
nomy/BIT_v4_ENG_LUGLIO_2017.pdf). The 18th census of the Italian Ministry of
Agricultural, Food and Forestry Policies (Official Gazette of the Italian Republic, General
Series no. 57 of 09/03/2018 – Ordinary Supplement no. 11) lists more than 4,800
traditional foods and beverages, the main pillars of the regional economies. Italy is the
European leader for foods and beverages with legal recognition status: 294 foods have the
status of DOP, IGP or STG, and 523 wines have DOCG, DOC or IGT. As declared by
UNESCO, the Mediterranean diet, mainly based on traditional foods and beverages, is an
Intangible Cultural Heritage of Humanity.
In 2016, the value of arable, fodder and tree crop production in Italy was
approximately 27 billion euros, half of the value of all agriculture, silviculture and fishery
sectors combined (CREA, 2017 https://www.crea.gov.it/wp-
content/uploads/2017/03/Itaconta-2016-x-WEB.pdf?x99213; the Italian Bioeconomy
strategy
http://www.agenziacoesione.gov.it/opencms/export/sites/dps/it/documentazione/S3/Bioeco
nomy/BIT_v4_ENG_LUGLIO_2017.pdf). Italy is a European leader in high-quality certified
agri-food products, with exports increasing from 33 to 41 billion euros since 2013. The
demand for high quality Italian agri-food products is increasing both in Europe and further
afield. Farmers, especially those producing high quality products, are paying increasing
18attention to sustainable solutions that adopt microbial-based fertilizing, N-fixing Rhizobia
(Mathu et al., 2012), plant growth-promoting, plant bio-conditioning and biocontrol
products (Bashan et al., Plant Soil 2014; Bashan et al., Biol Fertil Soils 2016). This interest
is markedly supported by the ongoing growth of organic farming in Europe and worldwide.
Despite recent concerns on the economic sustainability of organic farming and its impact
on forestry and biodiversity (Seufert et al., Nature, 2012), this market grew to 29.8 billion
euros in Europe in 2015, an increase of 13% over the previous year. Italy is one of the ten
largest world producers of organic products and has the second largest surface area
dedicated to organic farming in Europe, after Spain. In 2016, the Italian organic farming
surface area increased by 20% over 2015, amounting to 3.5% of the total world organic
farming surface area (1.8 M hectares), while 14.5% of the Italian surface was devoted to
agriculture (CREA, 2017 https://www.crea.gov.it/wp-content/uploads/2017/03/Itaconta-
2016-x-WEB.pdf?x99213).
In this context, microbiome studies may provide new insights that improve the
productivity of organic farming and overcome its limitations through the use of eco-
compatible solutions (e.g. microbial-based fertilizers, plant growth-promoting bacteria,
plant bio-conditioning and biocontrol products).
Microbiome relevance in terrestrial primary production. The soil/rhizosphere
microbiome mediates the cycle of carbon and other nutrients, affects the maintenance of
soil fertility and soil carbon sequestration and sustains plant growth (Figure 8).
Figure 8. The plant microbiome can be described as the sum total of the genomic
contribution made by the diverse microbial communities that inhabit the surface and
internal tissues of the plant parts. The microbial communities are mainly found in the
rhizosphere, endosphere and phyllosphere. The soil microbiome is the main source from
which the plant selects and builds its microbiome profile.
19Based on: Gopal M and Gupta A (2016) Microbiome Selection Could Spur Next-
Generation Plant Breeding Strategies. Front. Microbiol. 7:1971. doi:
10.3389/fmicb.2016.01971
All these activities have direct and indirect effects on plant and animal health in
terrestrial ecosystems and hence affect the quantity, quality and sustainability of primary
production (Amundson et al., Science 2015). Given the great heterogeneity of soil and the
fluctuating environmental conditions across microbial habitats (e.g. the rhizosphere,
preferential water flow paths, animal burrows and intra- and inter-aggregate
environments), there is no “typical” soil microbiome and the relative abundances of the
major bacterial and archaeal taxa can vary considerably within just a few centimetres
(Fierer et al., Nat Rev Microbiol 2017; Bulgarelli et al., Nature 2012).
The functions of soil microbes are still largely unknown. The available data suggest
that the soil microbiota is a complex and dynamic ecological community that interacts with
animals and plants and influences their physiology, health, production efficiency and
behaviour. Host fitness is determined by the microbiomes associated with the plant
rhizosphere and tissues in the root system and other plant organs. They support the
plant’s nutrition, health and resistance to biotic and abiotic stress. These microbiomes are
highly diversified and provide a plant-independent secondary genome that delivers key
ecological functions favouring the fitness of the plant host (Rosenberg, Zilber-Rosenberg,
MBio 2016). These interactions mean that the soil and plant microbiotas are key to the
quality and safety of plant primary production, including fruits, and related processed foods
(Gilbert et al., Proc Natl Acad Sci USA 2014; Marasco et al., Microbiome 2018). Italian
researchers have investigated microbial resources from desert and arid environments as
well as worldwide mycorrhizal fungi for the alleviation of abiotic plant stress.
The profile and functions of the microbiome in food-producing animals (Figure 9)
have been investigated in a number of species. The use of advanced molecular methods
in recent years has enabled a more detailed understanding of this area.
20Figure 9. Factors of animal physiology and development affected by the microbiome.
It is now clear that animals host a wide diversity of microbial communities that have
evolved alongside them as a result of complex and mutualistic interactions and play crucial
roles in their biology and health (Walter and Ley, Annu. Rev. Microbiol., 2011, Hooper et
al., Science, 2012). The gastrointestinal microbiota offers a typical example of such an
interconnected community (Hamady and Knight, Genome Res., 2009; Savage, Annu. Rev.
Microbiol., 2003; Gill et al., Science, 2006; Sender et al., Cold Spring Harbor Labs
Journals, 2016). However, the microbial communities of other anatomical sites have also
been characterized in recent years. These range from more obvious sites such as the skin
and the genitourinary tract, to less obvious ones such as the airways, and including areas
that were previously considered to be devoid of microorganisms, such as the placenta and
the fetus (Cao et al., 2014, Mor and Kwon, Am. J. Obstet. Gynecol., 2015). The aim is to
exploit this knowledge to facilitate the transition of livestock production from a system
strongly oriented towards maximizing productivity to a more efficient system that is less
dependent on the use of antibiotics, and hence more sustainable for the environment and
for society.
Although different species seem to partly share their microbiota (Milani et al., ISME J
2017), monogastric (e.g. pigs, chicken), ruminant (e.g. dairy cows, sheep) and lagomorph
(e.g. rabbits) animals have well distinguished ecosystems that have co-evolved with their
own microbiota and are characterized by species-specific enterotypes. This is due to their
different food sources (e.g. herbivorous vs. omnivorous) and feeding behaviours. Several
studies of rumen microbiota (Wallace et al. BMC Genomics 2015; Ben Shabat et al. ISME
J 2016) have investigated their evident symbiosis with ruminants and their role in
greenhouse gas production. However, there is a lack of information on pigs and poultry,
and no significant relationship between the gut microbiome and animal phenotypes has
yet been established (Stanley et al., Appl Microbiol Biotechnol 2014; Yuliaxis Ramayo-
Caldas et al., ISME J 2016). Nonetheless, the available data suggest that the livestock
21microbiota plays a significant part in the ultimate health, production efficiency and
behaviour of animals.
Relevance of microbiomes in marine primary production.
Fish is an invaluable source of food and nutrition that offers an income and livelihood
to communities worldwide. The worldwide fish consumption per capita reached 20 kg in
2014 thanks to the growth of aquaculture, which now provides half of all fish for human
consumption (FAO 2016).
The microbial communities found in marine sediment and seawater ecosystems are
numerically, taxonomically and functionally diverse (Figure 10).
Figure 10. Sustaining marine microorganisms: schematic view of macroorganisms,
and especially fish, as key contributors to the maintenance of microbial diversity.
Full arrows depict transfer of microbes through trophic processes and dashed arrows
depict microbial release from macroorganisms and passive processes. Grey arrows
correspond to the horizontal and/or vertical transfer potential of macroorganisms. Asterisks
on the abundance distributions represent two types of host-associated microbes:
symbionts/mutualists (blue) and opportunist copiotrophs (red). Question marks represent
ecosystem compartments for which there is currently insufficient data to generalize the
proposed mechanisms of the macroorganisms’ impact on microbial diversity. OTU =
operational taxonomic unit.
Based on: Troussellier M, Escalas A, Bouvier T and Mouillot D (2017) Sustaining
Rare Marine Microorganisms: Macroorganisms As Repositories and Dispersal Agents of
Microbial Diversity. Front. Microbiol. 8:947. doi: 10.3389/fmicb.2017.00947
22These communities are the primary contributors to marine/ocean biogeochemical
cycles and thus the drivers of other trophic levels, including aquatic animal production and
health (Moran, Science 2015). The marine microbiome responds to many natural and
anthropogenic environmental pressures (Bourlat et al., Mar Pollut Bull 2013; Goodwin et
al., Front Mar Sci 2017; Buttigieg et al., Curr Opin Microbiol 2018) and has been proposed
as an ecosystem indicator to assess the quality and productivity of seawater and
sediments (Nogales et al., FEMS Microbiol Rev 2011).
Few studies have investigated the role of the microbiome in fish health, physiology,
ecology and behaviour. Pioneering molecular studies have described the functional
diversity of the sea bream microbiome (Xing et al., FEMS Microbiol Ecol 2013; Ni et al.,
FEMS Microbiol Ecol 2014), the role of the microbiome in the developmental stages of fish
(Califano et al., Front Microbiol 2017) and how nutrition affects the gut microbiome and, in
turn, fish growth and efficiency (Parma et al., Anim Feed Sci Tech 2016; Piazzon et al.,
Microbiome 2017). Other studies have focused on developing effective strategies to
manipulate gut microbial communities through diet, to promote fish health and improve
productivity (Rimoldi et al., PeerJ 2018; Rimoldi et al., PLoS ONE 2018). Such strategies
could contribute to the goal of antibiotic-free aquaculture production.
While there is a growing market demand for high-quality fish products, competition
for land and water is increasing. Open-sea fish cages are thus key to the future growth of
aquaculture. In fact, the main issue with coastal aquaculture is benthic organic enrichment
caused by the settlement of solid waste (faeces and feed) on the seabed, which can lead
to eutrophication problems in enclosed and semi-enclosed coastal environments (Price et
al., Aquacult Environ Interact, 2015; Ballester-Moltó et al., Mar Environ Res 2017).
Ultimately, the loss of marine environmental quality also affects aquaculture fish quality
and productivity. Bioremediation technologies can be employed to prevent or mitigate such
consequences.
Relevance of microbiomes in food processing and nutrition. Microbes in food
and beverages are key factors in their ultimate quality, authenticity, nutritional properties,
safety and preservation. Food microbiomes derive from natural contamination from
primary food matrices and the environment (house microbiome) and from deliberately
added natural or commercial starters, which undergo pressures from stochastic,
deterministic and temporal drivers. Microbial fermentations are complex systems where
bacteria, yeasts and filamentous fungi communicate and interact. These microbial
contributions and activities enable raw materials to be processed into products with added
nutritional value. Microbial fermentation is the most natural, sustainable, low-cost,
functional and user-friendly biotechnology for the production of foods and beverages with
improved shelf life, safety, nutritional, functional and organoleptic properties and health-
promoting potential (Macori and Cottar, Curr Opin 2018; Filannino et al., Curr Opin
Biotechnol 2018) (Figure 11).
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